RNA processing mechanisms control lymphocyte development and activation

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One of the well recognised features of ageing is an increased susceptibility to infection that is caused by a decline in the function of the immune system. Our immune system forms during foetal development and the early neonatal period and is made up of many types of cells including the white blood cells. These are continuously replenished throughout the life-course from specialised stem cells called haematopoietic stem cells that are found in the bone marrow. The white blood cells can be further divided into lymphocytes and non lymphocytes. Amongst the lymphocytes are B cells which produce antibodies and specialised cells that kill virally infected cells. A class of lymphocyte that develops in an organ called the thymus is called the T cell and this cell co-ordinates the function of antibody producing and killer lymphocytes. One important feature of lymphocytes is that they hold a memory of previous encounters with infections. This has been used to create vaccines which make us immune to diseases without having to suffer the disease. While vaccines work well in young individuals they work poorly, or not at all, in the elderly. Because of the importance of lymphocytes they have been much studied and we have plenty of information on the different stages of development the cells go through as they mature and become stimulated by encounter with antigen (the technical term immunologists use for anything that stimulates the immune system). We know much about the signalling processes that take place inside the cell when receptors on the surface of lymphocytes are triggered. We also know much about a class of genes that encode proteins, called transcription factors, which act as on/off switches for genes in the DNA. Transcription factors convert the information encoded in the DNA sequence of genes into a message, called mRNA, which specifies the order in which amino acids are incorporated into proteins. Our project is aimed at understanding how the mRNA is regulated subsequent to its production. We suspect special proteins, called mRNA binding proteins, physically interact with the mRNA and control how long it remains in the cell and the rate at which it can give rise to new proteins. This type of regulation is called post-transcriptional control and is far less well understood. Our study will ask what the function of these mRNA binding proteins is in lymphocytes and will reveal how they work. Our gaol is to understand how mRNA binding proteins interact with signalling pathways and ultimately with transcription factors to control lymphocytes and the immune response.